Cyanide detoxification by the cobalamin precursor cobinamide. 2006

Kate E Broderick, and Prasanth Potluri, and Shunhui Zhuang, and Immo E Scheffler, and Vijay S Sharma, and Renate B Pilz, and Gerry R Boss
Department of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0652, USA.

Cyanide is a highly toxic agent that inhibits mitochondrial cytochrome-c oxidase, thereby depleting cellular ATP. It contributes to smoke inhalation deaths in fires and could be used as a weapon of mass destruction. Cobalamin (vitamin B12) binds cyanide with a relatively high affinity and is used in Europe to treat smoke inhalation victims. Cobinamide, the penultimate compound in cobalamin biosynthesis, binds cyanide with about 10(10) greater affinity than cobalamin, and we found it was several-fold more effective than cobalamin in (i) reversing cyanide inhibition of oxidative phosphorylation in mammalian cells; (ii) rescuing mammalian cells and Drosophila melanogaster from cyanide toxicity; and (iii) reducing cyanide inhibition of Drosophila Malpighian tubule secretion. Cobinamide could be delivered by oral ingestion, inhalation, or injection to Drosophila, and it was as effective when administered up to 5 mins post-cyanide exposure as when given pre-exposure. We conclude that cobinamide is an effective cyanide detoxifying agent that has potential use as a cyanide antidote, both in smoke inhalation victims and in persons exposed to cyanide used as a weapon of mass destruction.

UI MeSH Term Description Entries
D008658 Inactivation, Metabolic Reduction of pharmacologic activity or toxicity of a drug or other foreign substance by a living system, usually by enzymatic action. It includes those metabolic transformations that make the substance more soluble for faster renal excretion. Detoxication, Drug, Metabolic,Drug Detoxication, Metabolic,Metabolic Detoxication, Drug,Detoxification, Drug, Metabolic,Metabolic Detoxification, Drug,Metabolic Drug Inactivation,Detoxication, Drug Metabolic,Detoxication, Metabolic Drug,Detoxification, Drug Metabolic,Drug Inactivation, Metabolic,Drug Metabolic Detoxication,Drug Metabolic Detoxification,Inactivation, Metabolic Drug,Metabolic Drug Detoxication,Metabolic Inactivation
D003038 Cobamides Deoxyadenosinecobalamins,Vitamin B 12 Coenzymes,Vitamin B12 Coenzymes,B12 Coenzymes, Vitamin,Coenzymes, Vitamin B12
D003486 Cyanides Inorganic salts of HYDROGEN CYANIDE containing the -CN radical. The concept also includes isocyanides. It is distinguished from NITRILES, which denotes organic compounds containing the -CN radical. Cyanide,Isocyanide,Isocyanides
D004331 Drosophila melanogaster A species of fruit fly frequently used in genetics because of the large size of its chromosomes. D. melanogaster,Drosophila melanogasters,melanogaster, Drosophila
D006224 Cricetinae A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS. Cricetus,Hamsters,Hamster
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D014803 Vitamin B Complex A group of water-soluble vitamins, some of which are COENZYMES. B Vitamin,B Vitamins,Neurobion,Vitamin, B
D014805 Vitamin B 12 A cobalt-containing coordination compound produced by intestinal micro-organisms and found also in soil and water. Higher plants do not concentrate vitamin B 12 from the soil and so are a poor source of the substance as compared with animal tissues. INTRINSIC FACTOR is important for the assimilation of vitamin B 12. Cobalamin,Cyanocobalamin,Cobalamins,Eritron,Vitamin B12,B 12, Vitamin,B12, Vitamin
D015208 Smoke Inhalation Injury Pulmonary injury following the breathing in of toxic smoke from burning materials such as plastics, synthetics, building materials, etc. This injury is the most frequent cause of death in burn patients. Inhalation Injury, Smoke,Injury, Smoke Inhalation,Inhalation Injuries, Smoke,Injuries, Smoke Inhalation,Smoke Inhalation Injuries

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